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21.
In previous research, we found an independent interaction of alprazolam and caffeine in rats under acute dose regimens using two measures (reinforcement rate and shorter-response rate) of a differential reinforcement of low rate performance (DRL 45-s) in 3-h sessions. Applying the same behavioral endpoints, the present study investigated the alprazolam-caffeine interaction under chronic dose regimens. Both drugs were administered by the oral route. Acute alprazolam and caffeine dose-response curves (DRCs) were characterized and were then used to determine the maintenance dose for the respective chronic dose regimens. Both drugs decreased the reinforcement rate and increased the shorter-response rate in a dose-related fashion. An alprazolam DRC also was determined during chronic-caffeine, chronic-alprazolam, and concurrent chronic-caffeine-alprazolam dose regimens. Complete tolerance to caffeine-induced rate changes was observed on the second day. Incomplete tolerance occurred only at higher alprazolam doses (7–12.5 mg/kg). Cross tolerance was not found between alprazolam and caffeine. Upon discontinuation of both drugs, performance progressively returned to baseline. The four alprazolam DRCs as well as the effect-time profiles demonstrated that caffeine altered neither the magnitudes nor the patterns of alprazolam effects on the two rates under chronic dose regimens. The Pöch DRC method further confirmed the independent interaction of alprazolam and caffeine. Thus, the independence of the interaction held for both the acute and chronic dose regimens despite the development of tolerance in the latter regimens. 相似文献
22.
帕罗西汀治疗社交恐惧症的双盲对照研究 总被引:1,自引:0,他引:1
目的 比较帕罗西汀与阿普唑仑治疗社交恐惧症的疗效及安全性。方法 将 78例社交恐惧症患者按住院先后顺序分层随机法分为帕罗西汀组 4 0例及阿普唑仑组 38例 ,疗程均为 6周。疗效评定采用PRCA 2 4、CGI SI及临床四级疗效评定。安全性评价应用TESS、实验室检查及体检。结果 帕罗西汀组与阿普唑仑组疗效相当。帕罗西汀常见不良反应为恶心、头痛、口干、出汗、厌食等 ,不良反应程度均较轻 ,患者依从性好。结论 帕罗西汀治疗社交恐惧症安全、有效 ,患者对药物的耐受性及依从性均较好 相似文献
23.
Withdrawal from benzodiazepines in physically dependent rodents often requires that the drug be dislodged from its receptor
with a competitive antagonist. Withdrawal Seizure-Prone (WSP) mice were selectively bred for their susceptibility to handling-induced
withdrawal convulsions following chronic treatment with ethanol. Reflecting pleiotropic genetic influences, they also experience
more severe withdrawal from other sedative-hypnotics including the benzodiazepine, diazepam. We used this susceptible genotype
to test whether other benzodiazepine receptor (BZR) agonists also produce physical dependence following acute administration,
comparing studies of spontaneous withdrawal with those where convulsions were precipitated by a BZR antagonist (flumazenil).
Separate groups of mice were tested following a single injection of one of eight BZR agonists. Several doses of each drug
were tested for spontaneous withdrawal, and a single dose of each drug was tested for precipitated withdrawal. Withdrawal
convulsions were seen after all of the drugs by at least one method, suggesting that BZR agonists as a class elicit acute
physical dependence in this susceptible genotype.
Edited by Andrew Holmes 相似文献
24.
G. Cannizzaro A. Flugy C. Cannizzaro M. Gagliano M. Sabatino 《European neuropsychopharmacology》1993,3(4):477-484
Rats were treated for 5 weeks with three subconvulsant doses of picrotoxin (PTX) and pentylenetetrazol (PTZ) per week to induce a persistent reduction of the GABAA receptor function which results in chemical kindling. Fifteen days after termination of this treatment schedule, the effect of desipramine (DMI) and alpraxolam (ALP) on immobility time in the forced swim test (FST) was evaluated. Chronic PTX and PTZ did not alter the immobility time. Acute PTX and PTZ reduced the immobility of rats chronically treated with vehicle but not of those exposed chronically to PTX and PTZ. Chronic PTX did not influence the anti-immobility effect of DMI, but blocked that of ALP. Chronic PTZ markedly potentiated the anti-immobility effect of DMI but blocked that of ALP. Concomitant administration of chlordiazepoxide prevented the effects of chronic PTX and PTZ. These findings suggest that a long-lasting reduction in GABAA receptor function, unlike acute reduction, does not play an important role in the mobility of rats in the FST and in the anti-immobility effect of DMI while it blocks that of ALP. 相似文献
25.
Age-related increase in CNS sensitivity to benzodiazepines as assessed by task difficulty 总被引:1,自引:0,他引:1
Arlene M. Nikaido Everett H. Ellinwood Jr. Douglas G. Heatherly Samir K. Gupta 《Psychopharmacology》1990,101(1):90-97
The differential sensitivity of young and elderly healthy adults to the impairment effects of benzodiazepines was assessed by tasks with several levels of difficulty. Using a double-blind procedure, single doses of placebo, alprazolam (0.75 and 1.5 mg) and triazolam (0.25 and 0.5 mg) were ingested orally by 10 young men, 9 young women, 7 elderly men, and 10 elderly women. Order of drug administration was determined by a random Latin square design. Different versions of the subcritical tracking and digit symbol substitution tasks were characterized by three difficulty levels. Assessments of task performance were conducted at varying intervals for 7 h after drug administration. Both drugs induced a rapid initial onset of impairment in the two age groups. Evidence of increased drug sensitivity in the elderly was provided by the more prolonged duration of the pharmacologic effect in the older than young subjects, especially for the harder versions of the SCT and DSS tasks. In summary, the data provide support for the hypothesis of an age-related decline in the adaptive capacity to inhibit adverse drug effects. 相似文献
26.
In a double-blind, placebo-controlled, cross-over study, acute effects of suriclone — a cyclopyrrolone derivative — were investigated by means of topographic mapping of event-related potentials (ERPs). Fifteen normal volunteers, aged 22–35 years, received randomized, oral single doses of placebo, 0.1 mg, 0.2 mg and 0.4 mg suriclone and 1 mg alprazolam as a reference compound. ERPs were investigated in an auditory oddball paradigm before and 3 h after intake of each drug. In addition to 17 EEG leads, vertical and horizontal electro-oculograms (EOGs) were recorded. After EOG minimization and artifact identification, the peak latencies of the spatial average were determined by an automatic procedure. Compared to placebo, no significant effects of the low and middle doses of suriclone on N1 amplitude were observed; the highest dosage reduced N1 amplitude, as did 1 mg alprazolam to an even greater extent. While no consistent effects on P2 amplitude were observed after suriclone, alprazolam reduced P2 amplitude. P300 amplitude was reduced only after the highest dosage of suriclone, but much more so after alprazolam. P300 latency was not affected significantly by suriclone, but a marked prolongation of P300 latency was observed after 1 mg alprazolam. Concerning N1 and P2 effects, alprazolam, but not suriclone, may have an inhibitory influence on stimulus-induced cortical arousal. Concerning P300 effects, the used doses of suriclone were superior to 1 mg alprazolam, which seemed to have reduced cognitive information processing capacity and prolonged stimulus evaluation time. Self-rated well-being (adjective checklist) showed subtle beneficial effects after 0.1 mg and 0.2 mg, but marked sedative effects after both 0.4 mg suriclone and 1 mg alprazolam. 相似文献
27.
Eighteen non-anxious volunteers underwent sleep recordings and daytime tests of sleepiness, performance, and mood while receiving, either alprazolam 0.5 mg b.i.d. or diazepam 5 mg b.i.d. for 7 consecutive days. Recordings and tests were done before treatment and on the 1st and 7th days of treatment. Nocturnal sleep changes were similar for both groups; there were no statistically significant changes in mood. However, levels of daytime sleepiness differed. Alprazolam subjects showed more daytime sedation than diazepam subjects on treatment day 1, but showed a significant decreased in Day 1–7 daytime sedation. Although diazepam subjects were less sedated at the onset, they showed no tolerance to this effect; thus by treatment day 7, the two groups did not differ in levels of daytime sleepiness. Results suggested that tolerance to alprazolam's sedative effects (which develops during the 1st week of treatment) may be separable from tolerance to its antianxiety effects (which develops after at least 4 weeks). As daytime sedation is common and potentially dangerous with most anxiolytics, selective tolerance to this side effect is highly desirable. 相似文献
28.
Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers 总被引:1,自引:0,他引:1
Keh-Ming Lin John K. Lau Randall Smith Paul Phillips Edward Antal Russell E. Poland 《Psychopharmacology》1988,96(3):365-369
Single-dose pharmacokinetics of alprazolam was studied in 42 normal male volunteers (14 Caucasians, 14 American-born Asians, and 14 foreign-born Asians), after both oral and parenteral (IV) administration of a small dose (0.5 mg) of the test drug. Asians manifested significantly higher C
max, larger AUC, slower CL and longer t 1/2 under both testing situations. When body surface area was used as a covariate, these cross-ethnic differences remained statistically significant (except C
max) after oral but not IV drug administration. There were no differences between the two Asian groups in any of these parameters examined in this study. These results confirmed previous observations of ethnic differences in the pharmacokinetic response between Asians and Caucasians and suggested that smaller doses of alprazolam may be required for Asians for similar clinical effects as compared to their Caucasian counterparts. 相似文献
29.
目的比较帕罗西汀、阿普唑仑单一使用及早期联合使用治疗惊恐障碍急性期的临床疗效和安全性。方法将符合入组标准的90例惊恐障碍患者随机至为阿普唑仑组、帕罗西汀组和两药合用组各30例,为期12周。以临床判断和惊恐症状评定量表(PASS)、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)评定临床疗效,以副反应量表(TESS)评定药物不良反应。结果在治疗第1周末,阿普唑仑组及合用组PASS、HAMA、HAMD评分即出现明显改善,帕罗西汀组在第4周评分才开始有改善(HAMD为第3周),至治疗结束,3组间PASS总分差异无统计学意义;阿普唑仑组、帕罗西汀组及合用组有效率(%)及治愈率(%)分别为88.9,89.3,92.9,和59.3,60.7,60.7,差异无统计学意义;阿普唑仑组、帕罗西汀组不良反应发生率为51.9%和25%,而合用组仅为14.3%,明显低于前两组。结论阿普唑仑、帕罗西汀早期联合使用治疗惊恐障碍急性期快速、安全、高效,优于单一使用。 相似文献
30.
Huidobro AL Rupérez FJ Barbas C 《Journal of pharmaceutical and biomedical analysis》2007,44(2):404-413
The presence of a degradation product of alprazolam tablets that emerged throughout a short-stability assay has been determined and properly characterized. For this purpose an efficient methodology has been successfully applied, including SPE and HPLC methods for isolation and purification, respectively. LC/MS, MS/MS, 1H NMR, 13C NMR, UV and IR have been employed for structural elucidation confirming the identity of this impurity as 7-chloro-1-methyl-5-phenyl-[1,2,4]triazolo[4,3-a]quinolin-4-amine or triazolaminoquinoleine. The impurity, previously described as a long-term photodegradation product of alprazolam active pharmaceutical ingredient, was rapidly formed in the absence of light, but required the presence of excipients and its rate of formation increased with heat and humidity. In addition, a LC method has been developed and validated including triazolaminoquinoleine for the adequate determination of alprazolam and its mayor degradation product in tablets as pharmaceutical forms. 相似文献